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Back to the forum  Query: 2017-07-22 08:37 UTC (UTC+2h)
 
Yura
Regular

Belarus,
2017-03-29 08:31

Posting: # 17198
Views: 720
 

 alpha for RSABE [RSABE / ABEL]

Dear All
In "Draft Guidance on Progesterone" describes the calculation steps for HVD.
Tell me please, how to take into account of the alpha change when alpha is not present in the formulas?:-|
Best regards
d_labes
Hero

Berlin, Germany,
2017-03-29 12:33

@ Yura
Posting: # 17206
Views: 616
 

 alpha for RSABE

Dear Yura,

» Tell me please, how to take into account of the alpha change when alpha is not present in the formulas?:-|

don't get your point.
Can you please elaborate what you mean with "alpha change"?

Regards,

Detlew
Yura
Regular

Belarus,
2017-03-29 13:34

@ d_labes
Posting: # 17207
Views: 613
 

 alpha for RSABE

Dear d_labes
So, is it right: for ABEL I should adjust Type I Error (alpha) or in other words to decrease to 0.025? What I can do if I’ll use RSABE (because here alpha is absent in formula)?
d_labes
Hero

Berlin, Germany,
2017-03-29 14:23

@ Yura
Posting: # 17208
Views: 595
 

 adjusted alpha for RSABE

Dear Yura

» So, is it right: for ABEL I should adjust Type I Error (alpha)
To protect against an alpha-inflation which otherwise may occure, it's exactly what we recommend in our paper1.

» or in other words to decrease to 0.025?
That's not what we recommend in our paper. We recommend to adjust alpha based on the outcome of the study. For details see our paper, especially the examples.

» What I can do if I’ll use RSABE
Here I can't help since nobody has thoroughly investigated alpha inflation of the FDA recommended method for scaled ABE. This has to do with the controversies regarding where to locate the region of the type I error. See the paper of Davit et al.2

» (because here alpha is absent in formula)?
That's not correct.
Alpha is contained in the request to calculate 95% upper confidence limit of the linearized RSABE criterion. If you adjust alpha you have to calculate 1-alphaadj upper confidence limit. Looking at the SAS code change all alpha=0.1 to 2*alphaadj you will use.
But as already said: Nobody knows or can calculate the value of alphaadj to use.


  1. Labes D, Schütz H. Inflation of Type I Error in the Evaluation of Scaled Average Bioequivalence, and a Method for its Control. Pharm Res. 2016;33(11):2805–14. doi:10.1007/s11095-016-2006-1. full-text view-only
  2. Davit et al. "Implementation of a Reference-Scaled Average Bioequivalence Approach for Highly Variable Generic Drug Products by the US Food and Drug Administration"
    AAPS Journal, Vol. 14, No. 4, December 2012
.

Regards,

Detlew
Yura
Regular

Belarus,
2017-03-31 12:05

@ d_labes
Posting: # 17217
Views: 514
 

 adjusted alpha for RSABE

Thank you
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